title: Immune evasion and the evolution of molecular mimicry in parasites.
abstract: Parasites that are molecular mimics express proteins which resemble host proteins. This resemblance facilitates immune evasion because the immune molecules with the specificity to react with the parasite also cross-react with the host's own proteins, and these lymphocytes are rare. Given this advantage, why are not most parasites molecular mimics? Here we explore potential factors that can select against molecular mimicry in parasites and thereby limit its occurrence. We consider two hypotheses: (1) molecular mimics are more likely to induce autoimmunity in their hosts, and hosts with autoimmunity generate fewer new infections (the "costly autoimmunity hypothesis"); and (2) molecular mimicry compromises protein functioning, lowering the within-host replication rate and leading to fewer new infections (the "mimicry trade-off hypothesis"). Our analysis shows that although both hypotheses may select against molecular mimicry in parasites, unique hallmarks of protein expression identify whether selection is due to the costly autoimmunity hypothesis or the mimicry trade-off hypothesis. We show that understanding the relevant selective forces is necessary to predict how different medical interventions will affect the proportion of hosts that experience the different infection types, and that if parasite evolution is ignored, interventions aimed at reducing infection-induced autoimmunity may ultimately fail.
authors.affiliation: Department of Mathematics and Statistics, Queen's University, Kingston, Ontario, Canada; Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada; Department of Mathematics and Statistics, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada. ahurford@mun.ca.
authors.forename: Amy
authors.initials: A
authors.lastname: Hurford
authors.forename: Troy
authors.initials: T
authors.lastname: Day
mesh_terms: D000818:Animals; D005075:Biological Evolution; D003198:Computer Simulation; D006790:Host-Parasite Interactions / Q000276:immunology; D057131:Immune Evasion / Q000235:genetics / Q000276:immunology*; D018448:Models, Immunological; D018716:Molecular Mimicry / Q000235:genetics / Q000276:immunology*; D010271:Parasites / Q000276:immunology*; D012641:Selection, Genetic
keywords: Antigenicity; autoimmunity; clonal deletion; immunopathology; pathogen; within-host